Norine is the first database entirely dedicated to nonribosomal peptides (NRPs). In bacteria and fungi, in addition to the traditional ribosomal proteic biosynthesis, an alternative ribosome-independent pathway called NRP synthesis allows peptide production. It is performed by huge protein complexes called nonribosomal peptide synthetases (NRPSs). The molecules synthesized by NRPS contain a high proportion of nonproteogenic amino acids. The primary structure of these peptides is not always linear but often more complex and may contain cycles and branchings. In recent years, NRPs attracted a lot of attention because of their biological activities and pharmacological properties (antibiotic, immunosuppressor, antitumor, etc.). However, few computational resources and tools dedicated to those peptides have been available so far. Norine is focused on NRPs and contains more than 700 entries. The database is freely accessible at http://bioinfo.lifl.fr/norine/. It provides a complete computational tool for systematic study of NRPs in numerous species, and as such, should permit to obtain a better knowledge of these metabolic products and underlying biological mechanisms, and ultimately to contribute to the redesigning of natural products in order to obtain new bioactive compounds for drug discovery.

Nonribosomal peptides (NRPs) are molecules produced by microorganisms that have a broad spectrum of biological activities and pharmaceutical applications (e.g., antibiotic, immunomodulating, and antitumor activities). One particularity of the NRPs is the biodiversity of their monomers, extending far beyond the 20 proteogenic amino acid residues. Norine, a comprehensive database of NRPs, allowed us to review for the first time the main characteristics of the NRPs and especially their monomer biodiversity. Our analysis highlighted a significant similarity relationship between NRPs synthesized by bacteria and those isolated from metazoa, especially from sponges, supporting the hypothesis that some NRPs isolated from sponges are actually synthesized by symbiotic bacteria rather than by the sponges themselves. A comparison of peptide monomeric compositions as a function of biological activity showed that some monomers are specific to a class of activities. An analysis of the monomer compositions of peptide products predicted from genomic information (metagenomics and high-throughput genome sequencing) or of new peptides detected by mass spectrometry analysis applied to a culture supernatant can provide indications of the origin of a peptide and/or its biological activity.Nonribosomal peptides (NRPs) are molecules produced by microorganisms and synthesized by huge multienzymatic complexes (38, 41), called nonribosomal peptide synthetases (NRPSs). These megaenzymes are organized into modules, one for each amino acid to be built into the peptide product. This is accomplished by division of each catalytic step into specialized semiautonomous domains. The basic set of domains (adenylation, thiolation, and condensation) within a module can be extended by substrate-modifying domains, including domains for substrate epimerization, ␤ hydroxylation, N methylation, and heterocyclic ring formation. The peptide release is catalyzed by a thioesterase domain which can also, in many cases, be involved in an intramolecular reaction leading to a cyclic or partially cyclic peptide or, in fewer cases, in the oligomerization of peptide units (iterative biosynthesis). NRPs show a broad spectrum of biological activities and pharmaceutical applications. They can harbor antimicrobial, immunomodulator, or antitumor activities. Cyclosporine (5), an immunosuppressant drug widely used in organ transplantation, daptomycin (60) (marketed in the United States under the trade name Cubicin), used in the treatment of certain infections caused by Gram-positive bacteria, aminoadipyl-cysteinylvaline (ACV)-tripeptide, which is the precursor of cephalosporin and penicillin (29), the most famous antibiotic, and also bleomycin (57), used in the treatment of several cancers, are some common examples of NRPs of high therapeutic importance. Two main structural traits distinguish these peptides from ribosomally synthesized peptides: first, their primary structure is more frequently cyclic (partially or totally) branched or polycyclic rather than linear and, seco...